Experimental Medications: Monoclonal Antibody Medications

Rituxan is a monoclonal antibody (CD20, from mouse tissue) that binds to a receptor on the surface of B cells. These cells are then destroyed and their levels in the circulation are decreased. It is approved for use in the treatment of lymphomas, leukemias, and autoimmune disorders.

A Phase II trial, completed in 2006, examined the effect of a single course of Rituxan treatment in RRMS, with two infusions of 1,000 mg each, administered two weeks apart versus placebo. At 48 weeks, the number of active lesions was reduced by 91 percent and relapses were reduced by 58 percent, compared to a placebo group not taking any active medication. Twice as many people were taking the active medication versus those on placebo.

The drug was also tested in a study of 30 people with RRMS who had experienced continued clinical activity despite treatment with one of the approved disease-modifying therapies. Participants received two doses of Rituxan, two weeks apart, while continuing to take their usual medication. Results showed that gadolinium-enhancing lesions were reduced after treatment with Rituxan: 74 percent of post-treatment MRI scans were free of gadolinium-enhancing activity as compared with 26 percent who were free of gadolinium-enhancing activity at baseline. Overall, an 88-percent reduction was seen in the average number of these lesions compared to baseline scans.

A Phase I/II double-blind study of 80 people with SPMS, sponsored by the National Institute of Neurologic Diseases and Stroke, tested a combination of intravenous (IV) and intrathecal (IT) – which is given directly into the spinal fluid – rituximab versus placebo (the RIVITaLISe14 study). The study’s authors hypothesized that this combination method of Rituxan administration would cause more complete destruction of B cells both in the blood and the spinal fluid. Theoretically, the addition of the IT medication could be more effective for individuals with progressive MS in which the immune cells provoking the continued attack may reside exclusively in the central nervous system, without circulating through the blood.

The study enrolled 27 patients but analyzed data in an interim analysis from 22 of the participants (14 on active drug and nine on placebo) who had received at least two doses of the drug. While the study had originally aimed to measure progression of brain atrophy after two years of treatment, it was terminated early when the study authors did not find that the combination of IV and IT Rituxan was adequately decreasing B cells in the spinal fluid. Although multiple reasons might account for this finding (including lower doses of Rituxan used in this study than in previous studies), this study raises questions about rituximab’s ability to decrease active inflammatory cells in the central nervous system. Additionally, the small size of the study group did not allow for a true analysis of clinical outcome measures.

Serious adverse events have been reported in Rituxan-treated patients with other diseases, including rare cases of progressive multifocal leukoencephalopathy (PML), the same viral infection of the brain that has been seen with a small percentage of patients taking Tysabri. While no PML has been diagnosed in MS patients taking Rituxan, the number of individuals with MS treated with Rituxan is relatively small to date.

Rituxan is not likely to be further developed for FDA approval. However, next-generation anti-CD20 monoclonal antibodies have been developed to build on the encouraging data from Rituxan’s MS studies, including Ocrevus, which was approved in March 2017 and discussed earlier in the “Approved Medications” section.